How FDA's New RMAT Guidance Impacts Clinical, CMC Strategies

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FDA has issued a new draft guidance for industry, “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions,” that aims to provide sponsors involved in the development of such therapies with recommendations pursuant to certain sections of previously existing legislation, such as the Federal Food, Drug, and Cosmetic (FD&C) Act and the 21st Century Cures Act (1).

In short, what does this draft guidance mean?

Under section 506(g) of the FD&C Act, according to the draft made public by FDA on Sept. 25, 2025, a regenerative medicine therapy can be designated a regenerative advanced therapy, which FDA then refers to as a “regenerative medicine advanced therapy” (RMAT), if certain criteria are met (1).

Expedited programs are available to sponsors of those therapies that are designed to treat serious or life-threatening diseases or conditions, RMAT status among them (1). Other FDA designations in this vein include fast track, breakthrough therapy, priority review, and accelerated approval.

The draft guidance, in general, deals with regenerative medicine therapies regulated as biologics, under the FD&C Act, by FDA’s Center for Biologics Evaluation and Research (CBER) (1).

Does the guidance provide flexibility in clinical development?

FDA stated that CBER will consider trials that incorporate adaptive designs, enrichment strategies, and novel endpoints, providing as an example the area of advanced visual impairment. Here, an improvement in functional vision could be an acceptable endpoint, according to the draft (1). As another example, for tissue replacement products, short-term performance may be considered a clinically meaningful endpoint.

For RMAT-designated products, the guidance details pathways for accelerated approval based on surrogate or intermediate endpoints that are reasonably likely to predict long-term clinical benefit (1). The guidance specifies that sponsors may be able to use clinical evidence from patient registries, electronic health records, or other sources of real-world evidence in place of traditional confirmatory trials.

Have any therapies of note received RMAT designation recently?

In July 2025, the clinical-stage biotechnology company Genascence Corporation announced that its potential first-in-class gene therapy blocking interleukin 1 for the treatment of knee osteoarthritis was granted RMAT designation, after FDA had previously given the therapy fast track designation in 2024 (2).

A second clinical-stage company, VeonGen Therapeutics, then announced in August 2025 that FDA gave RMAT status to VG801, VeonGen’s lead investigational gene therapy for Stargardt disease and other retinal dystrophies associated with mutations in the ABCA4 gene (3).

What about chemistry, manufacturing, and controls (CMC) considerations?

The guidance makes clear that accelerated clinical timelines should not reduce CMC standards required for approval (1). Sponsors must provide sufficient CMC information to ensure product quality, including identity, purity, and strength. The document acknowledges the unique challenge of aligning rapid product development with faster clinical programs for regenerative therapies.

The guidance emphasizes the importance of early and frequent interactions with CBER's Office of Therapeutic Products to proactively address manufacturing challenges. For RMAT designation, preliminary clinical evidence must be generated with a product comparable to the one intended for later-stage development, underscoring the need for robust comparability data when manufacturing changes occur (1).

The comment period for the draft guidance is open through Nov. 24, 2025 (4).

References

1. FDA, Draft Guidance for Industry, Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (CBER/OTP, September 2025).
2. Haigney, S. FDA Grants Regenerative Medicine Advanced Therapy Designation to Gene Therapy for Knee OA. BioPharmInternational.com, July 18, 2025.
3. Lavery, P. VeonGen’s Stargardt Disease Gene Therapy Gets FDA RMAT Status. BioPharmInternational.com, Aug. 22, 2025.
4. FDA, “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Draft Guidance for Industry; Availability,” Notice, Federal Register, 90 FR 46225, 46225–46227.